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The article presents the modern views of clinicians and geneticists on one of the most severe genetic disorders of skeletal and connective tissues - osteogenesis imperfecta. The review provided the literature data that showed the incidence rates, genetic heterogeneity of osteogenesis imperfecta, as well as the role of some proteins involved in the construction of bone tissue, as well as a clinical classification of the main types of the disorder. The authors described a clinical case: a girl with typical clinical and radiological manifestations of the rarest of all types of osteogenesis imperfecta - type II (perinatal-lethal, congenital osteogenesis imperfecta, Vrolik’s syndrome). The child’s diagnosis was verified by a parallel DNA sequence analysis which showed a heterozygous mutation in exon 29 (c.1966G> A) of COL1A1 gene not previously described in the literature. It caused the substitution of glycine for serine at position 656. The role of antenatal diagnostics and the importance of medical genetic counselling of the family before planning the next pregnancy due to the existing risk of re-birth of a sick child is outlined. Due to the fact that majority of the patients with the most prognostically unfavourable type II osteogenesis imperfecta, as a rule, die in utero, the described case of observation of the girl with typical clinical and X-ray signs of the disorder for almost 3 months of postpartum period is extremely rare and highly indicative. The detection of the heterozygous mutation in exon 29 (c.1966G > A) of COL1A1 gene by a parallel DNA sequence analysis which was not previously described in the literature gives an additional significance to the described observation.

Urinary tract infections are a common global problem among physicians of various specialties, including therapists, pediatricians, nephrologists and urologists. Today UTI is one of the leading bacterial infections in both adult and child populations. The main type of therapy and prevention of recurrent UTI is the use of drugs with an antibacterial effect (antibiotics, uroseptics). An urgent problem in modern medical practice is the increasing antibiotic resistance, which requires the development of new approaches to therapy and prevention, including UTI. In recent years, special attention has been paid to the study of vitamin D receptor (VDR) gene polymorphisms as a possible risk factor determining the predisposition to a number of infectious and noninfectious diseases. More than 200 polymorphisms of the VDR gene have been identified, four of which – FokI, BsmI, ApaI, and TaqI – are particularly common. Different VDR alleles can cause small changes in receptor function, which can affect resistance or susceptibility to a particular infection. The review presents data from modern studies demonstrating the relationship between vitamin D supply and development, the frequency of recurrence and the nature of the course of UTI. In one study, vitamin D has been shown to enhance the cathelicidin-mediated antibacterial action of bladder epithelial cells. It also demonstrated the currently known defense mechanisms of vitamin D against urinary tract infections, including its effect on components of the innate immune system.

To date, the most discussed issue is the rational dosage and duration of cholecalciferol preparations course for the correction and prevention of hypovitaminosis D. Objective of the research: to compare the structure of provision and the median 25 (OH) D before (2013–2016) and during the introduction into clinical practice (2018–2019) of the National Program Vitamin D Deficiency in Children and Adolescents in the Russian Federation: Modern approaches to correction» in young children. Materials and methods: the study had two stages. The first stage took place as a part of the RODNICHOK2 study from 2013 to 2016 before the implementation of the National Program «Vitamin D Deficiency in Children and Adolescents in the Russian Federation: Modern Approaches to Correction». The second stage of the study took place in 2018–2019 during the implementation of the National Program in clinical practice. The study participants were 246 children aged from 1 month to 3 years who took cholecalciferol preparations. The assessment of calcidiol concentration in the blood serum was assessed by the method of chemiluminescence immunoassay (CLIA) using reagents Liaison® 25OH Vitamin D Total Assay on the Liaison Dia Sorin Pleutschland GmbH device in the centralized laboratory of Scientific Center EFIS Ltd, Moscow. Results: during the introduction into clinical practice of the National Program, the frequency of prescribing a dosage of 500 IU/day significantly decreased to 4,9% (χ2=80,4, p

Differential diagnosis of hypoglycemic syndrome remains an urgent problem in Pediatrics. In this article, a case of glycogen storage disease (BNG) type 0 is described in the boy, which is undoubtedly a rare pathology, which makes it difficult to diagnose this form of glycogenosis. In this description, the case of type 0 BNG is caused by a mutation in the GYS2 gene encoding the hepatic isoform of glycogen synthase. This form of the disease is usually asymptomatic in infancy. However, it can be suspected in the case when the refusal of night feeding causes certain difficulties due to the hungry ketotic hypoglycemia that occurs in the child. The first clinical symptoms appear in early childhood with the inclusion of a more varied diet in the child, increasing the intervals between meals. Symptoms of the disease are primarily caused by hypoglycemia. It should be noted that, despite the low levels of glycemia, most children do not have any mental development disorders, since the increase in the level of ketone bodies in the blood plasma provides the brain with an alternative source of energy.

Introduction . Data on the vitamin D receptors (VDR) found on the surface of a large number of cell types of the human body were first published several decades ago, which served as a prerequisite to study the role of vitamin D in the development of some diseases, including infections. Objective of the study . Evaluate the relationship between administration of cholecalciferol supplements, the synthesis of defensins, and the incidence and morbidity patterns of acute respiratory infections (ARI) in young children. Material and methods. 108 healthy children aged 1 month to 3 years were examined, of which 34 (31.5%) were vitamin D sufficient, 40 (37.0%) had a vitamin D insufficiency, 27 (25.0%) had a vitamin D deficiency and 7 (6.5%) children had severe vitamin D deficiency. After the course of treatment of vitamin D deficiency with therapeutic doses, all patients were prescribed prophylactic doses of cholecalciferol supplements (1000 IU/day) for a 6-month course. Results. Therapeutic doses of cholecalciferol promoted β 1 and β 2-defensin expression; a direct correlation was found between the daily dose of vitamin D and the increase of β 2-defensin expression (r = 0.34, p

Introduction. Vitamin D plays a fundamental role in the regulation of calcium and phosphorus homeostasis, and in recent decades its non-calcemic effects have been intensively studied.The aim of the work was to analyze the patterns of vitamin D availability in young children against the background of prolonged use of an aqueous solution of cholecalciferol in preventive doses.Materials and methods: 192 children of the first three years of life were examined (Arkhangelsk – 77 (40.1%), Moscow – 38 (19.8%), Stavropol – 77 (40.1%) children). Assessment of vitamin D availability was carried out by the level of serum calcidiol (25(OH)D). Based on the initial vitamin D supply, patients were divided into groups, and participants used cholecalciferol preparations for 30 days.Results. The baseline vitamin D supply was 26.0 (19.5–35.4) ng/ml. Median 25(OH)D in children in the Moscow region is higher than in Arkhangelsk and Stavropol (pConclusion. The used prophylactic dosage of 1000 IU/day of an aqueous solution of cholecalciferol was effective in most compliance children. The elimination of deficiency and the prevention of vitamin D deficiency is most effective when used for 6 months or more.

Introduction. Coeliac disease is a genetically determined disease associated with the HLA-DQ2 and DQ8 genes. According to European data, these alleles are detected in more than 95% of patients. The results of earlier studies in various regions of the Russian Federation and the constituent republics have shown a lower incidence of HLA-DQ2/DQ8 in children with coeliac disease (60–80%). These data served as a basis for discussion about regional genetic features and the potential for disease development in a significant proportion of patients without DQ2/DQ8 alleles.Methods. Genetic screening was conducted on 275 children with coeliac disease. According to the results of the study, the patients were assigned to genetic risk groups.Results. HLA-DQ2/DQ8-alleles were detected in 274 children (99.6%), with 86.9% of patients having DQ2 molecule in genotype and 12.7% having DQ8 molecule. Among 239 DQ2-positive patients, 33.5% were DQ2 homozygous. The remaining DQ2-positive patients had the following HLA-DR-DQ allele distribution: DR3-DQ2/DR5-DQ7 – 8.7%, DR7-DQ2/DR5-DQ7 – 13.4%, DR3-DQ2/ DRx-DQx – 22.2%, DR7-DQ2/DRx-DQx – 2.2%. In five children the incomplete DQ2 molecule was determined, represented by DQA1*0501 allele, while in four patients DQA1*501 was associated with DQB1*0301 allele forming DR5-DQ7 molecule. We found high and significant risk alleles in 29.1% and 22.2% of cases, while moderate and low risk alleles were found in 27.3% and 21.4% of cases respectively.Conclusions: In Russian children with coeliac disease the prevalence of HLA-DQ2/DQ8 alleles corresponds to European data. Low detection frequency of HLA-DQ2/DQ8 molecules in Russian coeliac patients, which was reported earlier, may be due to peculiarities of the approach to the disease diagnostics, which do not correspond to modern Russian and international recommendations.

Relevance: immunotropic effects of cholecalciferol are caused by vitamin-D-induced synthesis of antimicrobial peptides (AMP), in particular р-defensins. There are very few studies in pediatric clinical practice confirming the effect of vitamin D availability on AMP synthesis. Aim: analysis of the correlation between vitamin D availability and AMP production and assessment of the effect of cholecalciferol medication intake on defensin synthesis in young children. Materials and methods : 108 healthy children aged 1 month to 3 years were examined, of which 34 (31.5%) were adequately provided with vitamin D (calcidiol level over 30 ng/ml), 40 (37.0%) with insufficiency (20 to 30 ng/ml), 27 (25.0%) with vitamin D deficiency (10 to 20 ng/ml) and 7 (6.5%) with severe deficit (less than 10 ng/ml). In the presence of hypovitaminose of vitamin D the monthly course of cholecalciferol in doses of 2000-4000 lU/day was prescribed for correction, and in normal provision -prophylactic administration of 1000 IU/day. The indices of 25(ON)D, β1- and β2-defensins were determined three times. Results. On natural feeding, the rates of β1-defensin are 2.3 times (p

Objective: The objective is a comparative analysis of vitamin D content and level of proinflammatory cytokines in infants born by mothers with endocrine disorders, and in infants of women with normal body weight.Methods: The clinic-anthropometrical and laboratory observation of 78 children born in Stavropol Regional Clinical Perinatal Centre: 36 infants were born by women with obesity and 18 – by women with gestational diabetes mellitus associated with obesity, 24 – by women who did not have obesity and clinical and laboratory signs of intolerance to glucose (control group). The level of calcidiol and interleukin 1β and 6 were determined in blood serum.Results: The content of vitamin D in infants born by healthy women was higher than in infants born by mothers with gestational diabetes mellitus associated with obesity and by mothers with obesity. Infants born by mothers with obesity had higher level of proinflammotary cytokines than those of control group.Conclusions: Children, born by mothers with endocrine disorders, have lower level of calcidiol and require postnatal prevention of vitamin D deficiency. Also it is necessary to take vitamin D during the pregnancy to prevent complications in pregnancy and neonatal pathology.

Patients on a gluten-free diet are at risk of developing polyhypoavitaminosis and deficiency states, which requires the supplementation of their diet to prevent nutrient deficiencies. The aim of the study: to analyze the dynamics of anthropometric and laboratory parameters, components of the quality of life in children with coeliac disease on the background of a month-long course of administration of hypercaloric mixture for enteric nutrition. Materials and methods: 45 children with coeliac disease aged 2-10 years (mean age 6.3 ± 0.3 years) on a strict gluten-free diet for more than one year. All patients received additional enteric nutrition with a hypercaloric mixture in the volume of 200 ml/day (300 kcal/day) for 1 month as a supplement to the main food ration. Two groups of patients receiving the supplement in 2012-2013 and 2017-2018 were identified. Physical development was assessed under the WHO AnthroPlus programme. The quality of life indicators were assessed using the PedQL 4.0 questionnaire. Results: the total frequency of protein-сalorie deficiency (PCD) before the course of nutritional supplementation was 13 (28.9%) cases, while acute PCD was diagnosed in 6 (13.3%) and chronic PCD in 7 (15.6%) patients. Against the background of the course of nutritious supplementation in children with coeliac disease, there was a significant reduction in weight, height and BMI in both groups. Patients in 2012-2013 initially had a greater gap in weight and height compared to children in 2017-2018. There was an improvement in the sum of the quality of life indicators by 6.3% for children in the first group and by 4.3% for children in the second group against the background of nutritional supplementation. Conclusions: Enrichment of children’s diets with a hypercaloric blend of dietary fiber helps to accelerate the pace of physical development, reduce the number of children with diabetes mellitus, improve hemogram rates and most components of quality of life.

The article presents the results of vitamin D tests in children with cystic fibrosis and in healthy children living in the South of Russia. The study showed the high prevalence of vitamin D deficiency and inadequate levels in patients with cystic fibrosis (86.7%). 25(OH) D level characterizing the vitamin D status decreases progressively in patients and healthy children. With regard to the above mentioned, it is significantly lower in patients with cystic fibrosis than in healthy children in all age periods. The correlation between the serum calcidiol level and the age of patients with cystic fibrosis was r = -0.44 (p = 0.015). Intake of prophylactic (500--1000 IU/day) and therapeutic (1500--3000 IU/day) doses of cholecalciferol results in a less significant increase in calcidiol levels in patients with cystic fibrosis compared with healthy children. A significantly lower 25(OH)D level was detected in patients with cystic fibrosis infected withStaph. aureus.The 25(OH)D levels are significantly lower in children with cystic fibrosis and hypocholesterolemia, than in patients with normal cholesterol levels. Risk factors for the development of severe hypovitaminosis D in children with cystic fibrosis are age, physical developmental delay, exocrine pancreatic insufficiency, presence of chronicStaph. Aureusbronchopulmonary infection. Given the conducted study, the dosage of cholecalciferol in patients with cystic fibrosis should be at least 2 times higher than that in healthy children.

With antibiotic resistance increasing and new microbial resistance factors forming, the problem of creating new methods to treat and prevent the urinary tract infections becomes topical. The latest studies showed that urothelium contains a large number of immune factors providing its protection against the adverse effects of various uropathogens in vivo. There are very promising molecules – antimicrobial peptides (AMPs) – in terms of further therapeutic use among the components of inborn immunity. AMPs are the evolutionarily oldest molecules of innate immunity. The article discusses current data on the presence of various classes of AMPs in the urinary system, demonstrates data on their effectiveness as therapeutic agents against UTI, and describes further prospects for their use in the GP practice.

Due to the growth of non-infectious morbidity of the world’s child and adult population, the concept of nutritional programming connecting cardiovascular and certain endocrine diseases with the fetoplacental complex disorders in the antenatal period has been developed over the past 25 years. An increase in the prevalence of obesity and gestational diabetes in pregnant women lays the groundwork for an increase in the prevalence of glucose metabolism disorders and the risk of endocrine pathology in children. Both low weight and overweight at birth evidence the unfavourable course of the intrauterine period. The review discusses the factors contributing to the fetal organs and systems growth retardation, hypovitaminosis D, insulin resistance and possible mechanisms for their development. The authors present the analysis of the data available in the modern literature on the mechanism of the obesity and GDM programming effect on the diseases in new-borns and children.

Acetaminophen (AAP) is one of the most common and widely used antipyretic drugs, but its overdose is the leading cause of fulminant hepatic insufficiency in the world. Mechanisms of liver damage at the use of toxic doses of AAP are caused by the transformation of the isoform of cytochrome P450 (CYP2E1, CYP2A6) into a reactive metabolite, N-acetyl-parabenzoquinonimine (NAPQI), which plays a major role in hepatotoxicity. Another mechanism of hepatotoxicity includes the formation of peroxynitrite – a toxic free radical produced in the mitochondria, which causes oxidative damage. In addition to liver damage in case of acetaminophen poisoning, nephrotoxic effect can occur. Potential mechanisms of nephrotoxicity in overdose of AAP are presented, caused by cytochrome P450, as well as prostaglandin synthetase and enzyme N-deacetylase are described. In the clinical case described by us, the development of fulminant hepatic insufficiency against the background of acetaminophen administration led to the development of a coma along with the kidney damage, however, a stable positive dynamics, was achieved during treatment. In the catamnesis 2.5 years later, there were no signs of fibrosis or cirrhosis of the liver.

The literature data and the finding of our studies on the analysis of the correlation between the level of parathyroid hormone and supply of vitamin D of children (n=107) of early age are presented in the article. The serum level of vitamin D in the analyzed group of children was 24.8 [17.6–32.5] ng/ml, the median of the parathyroid hormone was 21.0 [12.3–25.5] pg/ml. It has been established that children with optimal supply of vitamin D have significantly lower parathyroid hormone levels vs. the children with vitamin D insufficiency (25 (OH) D from 20 to 30 ng/ml) and deficiency (calcidiol values below 20 ng/ml). The correlation between the level of vitamin D and parathyroid hormone was r=-0.18, p=0.035. The best supply of vitamin D was found in children of the first year of life – 25 (OH) D concentration was 29.95 [16.2–40.3] ng/ml. The parathyroid hormone level (16.5 [10.7–23.8] pg/ml) in these children was reliably lower (p=0.05) vs. the children of the second and third years of life. A positive correlation was established between the age of patients and the parathyroid hormone level (r=0.2, p=0.05). Preventive doses of vitamin D were received by 42.1% of children. The blood serum concentration of 25 (OH) D in them was higher (32.7 ng/ml), and the parathyroid hormone level was significantly lower (14.9 pg/ml) vs. the children who did not receive cholecalciferol preparations (p

Medical examination of 360 children from four regions of Russia (Moscow, Astrakhan, Stavropol, Kazan) showed significant regional differences in the sufficiency and compensation of vitamin D deficiency at the baseline (Day 0) and established factors associated with vitamin D sufficiency on Day 0. The established interregional differences in vitamin D levels were not due to insolation, but primarily to adequate vitamin D supplementation received at the baseline. Vitamin D supplementation (an average of 894 ± 632.6 IU/day) significantly reduced the risk of vitamin D deficiency (RR 0.15, 95% CI 0.09–0.26, P = 5.7 x 10 –14 ). The study included the analysis of factors associated with the increase in 25(OH)D levels during the administration of Aquadetrim, identification of predictors of patient’s response and the analysis of identified predictors. The most important factor determining the patient’s response was the dose of vitamin D taken by the patient: 25(OH)D levels increased by 1 ng/ml with an increase in the dose of vitamin D by 90 IU per day. As can be seen from the above, the study results indicate that the vitamin D deficiency requires a long-term preventive therapy (for at least several months) with adequate doses of vitamin D (1000–2000 IU/day).

Schoolchildren and their state of health, in particular, deficiencies, deserve no less attention than children of early age, while the recognition of the existence of inadequate vitamin D sufficiency in children of all age groups has not yet led to the introduction of mass prophylaxis for hypovitaminosis D. There are a number of factors determining the concentration of 25(OH)D-calcidiol in the blood. However, it is obvious that among many factors one should focus on several most significant and develop a scheme for correcting deficiency in each region.Purpose: to assess vitamin D sufficiency in adolescents living in Moscow, to correct calcidiol status in adolescents on the basis of baseline concentration of the metabolite transported in the blood. Material and methods: 769 adolescents aged 11-18 years for whom 25(OH)D concentration in the blood was evaluated, then 218 patients were randomized into 2 groups: the study group received tableted dietary supplement Minisun® vitamin D3, the controlgroup received placebo. The dosage of cholecalciferol was defined based on the initial level of calcidiol in patients. The study continued for 6 months, then blood was re-sampled to determine the level of calcidiol.Results: the study found low sufficiency with calcidiol among the schoolchildren: 25(OH)D median was 16.3 [11.4-20.8] ng/ml, only 5.2% of patients had normal concentration of calcidiol in the blood. At the second examination, positively significant differences in the status of vitamin D were observed in the study compared to the control group, while patients in the study group,against a background of cholecalciferol donation, demonstrated 25(OH)D median increase from 16.2 [12.25-19.3] ng/ml to 24.2 [21.05-26.4] ng/ml (p

The review presents information about the pathophysiological mechanisms underlying disorders of the processes of mineralization of bone tissue in patients with celiac disease. The attention is focused on the role of vitamin D and its active metabolite calcitriol, and also parathyroid hormone in regulating calcium-phosphorus metabolism, which is carried out in target organs – small intestine, kidney, bone tissue. Atrophy of the intestinal mucosa in celiac disease is accompanied not only by malabsorption of calcium, and increased resorption of bone due to increased concentration of PTG. According to various studies on the background of developing the osteoporosis in celiac disease, the risk of bone fractures is significantly increased in patients. Strict adherence to a gluten-free diet allows to normalize both the absorption of calcium, and impaired hormonal mechanisms in bone remodeling in the acute phase, and can reduce the risks of osteoporosis and pathological fractures in patients with celiac disease.

The study estimated vitamin D provision for babies in relation to the type of their feeding and the efficiency of drug donations of cholecalciferol preparations. A total of 132 babies aged 1 to 12 months were examined. Vitamin D deficiency was shown to occur in more than half (58.3%) of the babies at the solar minimum. If hypovitaminosis D was not prevented using drugs, the serum 25(OH)D level in the breastfed babies was 8.7 (6.3-14.8) ng/ml, which was significantly lower than that in formula-fed ones [24.55 (19.0-32.0) ng/ml] (p=0.00002). Cholecalciferol taken by the infants in a preventive dose of 500-1500 IU/day substantially increased their provision with vitamin D from 19.8 (10.4–26.3) to 32.7 (24.5-45.7) ng/ml (p=0.0000007), regardless of the feeding pattern. The serum calcidiol level is closely correlated with the dose of cholecalciferol (r=0.57; p

Background: Vitamin D insufficiency is a widespread phenomenon, having an adverse effect on human health. This problem is also actual in Russia, which most part of the territory is located above the 42nd latitude and is at risk for vitamin D insufficiency. Objective: Our aim was to evaluate the vitamin D sufficiency of the child population of a junior age group and the adequacy of a drug treatment/ prevention of vitamin D insufficiency in various regions of the Russian Federation. Methods: Children of the first 3 years of life, who received in-patient treatment in medical institutions of Russia, were examined. When they were involved in the study, they took a blood test to determine a plasma 25(OH)D concentration. The study period: November, 2013 – October, 2014. Results: 1,230 children aged from 1 month to 3 years were examined. Vitamin D insufficiency (25(OH)D concentration in the blood plasma 21–29 ng/ml) is found in 300 (24.4%), deficiency (25(OH)D < 20 ng/ml) — in 513 (41.7%) children. The prevalence of vitamin D insufficiency and deficiency did not depend on a geographical location and level of insolation of regions, where the surveyed lived. Conclusion: In the studied selection more than 2/3 of children of a junior age group have a vitamin D insufficiency or deficiency. In this regard, it is expedient to revise the current guidelines taking into account modern approaches to the prevention and treatment of a vitamin D insufficiency, to make the appropriate changes and to implement them in a clinical practice.